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Combined effects of the p53 and p73 polymorphisms on lung cancer risk.

Publication ,  Journal Article
Schabath, MB; Wu, X; Wei, Q; Li, G; Gu, J; Spitz, MR
Published in: Cancer Epidemiol Biomarkers Prev
January 2006

Lung cancer is a multigenic disease where one variant single nucleotide polymorphism may have only a modest independent effect on the disease phenotype, yet in aggregate, multiple biologically relevant single nucleotide polymorphisms may provide a more accurate representation of risk. Polymorphisms in members of the p53 family, such as p53 and p73, that have a functional relevance would be predicted to contribute to the disease phenotype. In this analysis, we used genotype data from 863 lung cancer cases and 852 healthy controls to test for multigenetic effects of polymorphisms at p53 exon 4, introns 3 and 6, and at p73 exon 2. All individuals in this analysis were self-reported non-Hispanic Caucasians. When the p73 and p53 variant alleles were combined and analyzed as a continuous variable, there was a 13% increase [odds ratios (OR), 1.13; 95% confidence intervals (CI), 1.05-1.21] in lung cancer risk for each additional variant allele. Furthermore, when the number of variant alleles was categorized into three groups (zero, one to three, and four or more variants), there was evidence of a gene-dosage effect with increased risks for individuals with one to three variants (OR, 1.30; 95% CI, 1.05-1.61) and four or more variants (OR, 1.78; 95% CI, 1.23-2.56). When the data were stratified by smoking status, an increased risk for lung cancer was evident only in current (OR, 2.32; 95% CI, 1.25-4.33) and former smokers (OR, 1.73; 95% CI, 1.02-2.94) with four or more variants. Younger individuals with four or more variants were also at a significantly increased risk for lung cancer (OR, 3.15; 95% CI, 1.62-6.12). This study provides support for the multigenetic effects of variant alleles from p53 exon 4, and introns 3 and 6, and p73, and their interplay with smoking, resulting in a significantly increased risk for lung cancer in this Caucasian population.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

January 2006

Volume

15

Issue

1

Start / End Page

158 / 161

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Protein p73
  • Smoking
  • Risk
  • Polymorphism, Genetic
  • Odds Ratio
  • Nuclear Proteins
  • Middle Aged
  • Male
  • Lung Neoplasms
 

Citation

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Chicago
ICMJE
MLA
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Schabath, M. B., Wu, X., Wei, Q., Li, G., Gu, J., & Spitz, M. R. (2006). Combined effects of the p53 and p73 polymorphisms on lung cancer risk. Cancer Epidemiol Biomarkers Prev, 15(1), 158–161. https://doi.org/10.1158/1055-9965.EPI-05-0622
Schabath, Matthew B., Xifeng Wu, Qingyi Wei, Guojun Li, Jian Gu, and Margaret R. Spitz. “Combined effects of the p53 and p73 polymorphisms on lung cancer risk.Cancer Epidemiol Biomarkers Prev 15, no. 1 (January 2006): 158–61. https://doi.org/10.1158/1055-9965.EPI-05-0622.
Schabath MB, Wu X, Wei Q, Li G, Gu J, Spitz MR. Combined effects of the p53 and p73 polymorphisms on lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):158–61.
Schabath, Matthew B., et al. “Combined effects of the p53 and p73 polymorphisms on lung cancer risk.Cancer Epidemiol Biomarkers Prev, vol. 15, no. 1, Jan. 2006, pp. 158–61. Pubmed, doi:10.1158/1055-9965.EPI-05-0622.
Schabath MB, Wu X, Wei Q, Li G, Gu J, Spitz MR. Combined effects of the p53 and p73 polymorphisms on lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):158–161.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

January 2006

Volume

15

Issue

1

Start / End Page

158 / 161

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Protein p73
  • Smoking
  • Risk
  • Polymorphism, Genetic
  • Odds Ratio
  • Nuclear Proteins
  • Middle Aged
  • Male
  • Lung Neoplasms